Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type 1 antineuronal nuclear autoantibody (ANNA-1, also known as "anti-Hu") is a marker of neurologic autoimmunity that is highly associated with small-cell lung carcinoma (SCLC). To determine the spectrum of symptoms and signs as well as the frequency of cancer in adult patients who are seropositive for ANNA-1, we reviewed 162 sequential patients (67% female) identified as ANNA-1-positive in a comprehensive immunofluorescence screening test. In 21% of these patients, the antibody test requested by the physician was not ANNA-1. By the end of the follow-up period, cancer had been found in 142 patients (88%). Ten of these lacked evidence of SCLC (4 had prostate carcinoma, 3 breast carcinoma, 1 both prostate carcinoma and melanoma, 1 lymphoma, and 1 squamous-cell lung carcinoma). Of the 132 patients (81%) with proven SCLC, 17 had one or more coexisting malignant neoplasms (6 had renal carcinoma, 4 another lung primary carcinoma, 3 prostate carcinoma, 3 breast carcinoma, and 4 assorted neoplasms). The diagnosis of SCLC in 128 patients (97%) followed the onset of paraneoplastic symptoms. SCLC was identified in 10 patients by chest MRI after an equivocal chest radiograph or CT; in 28 by bronchoscopy, mediastinoscopy, or thoracotomy; and in 7 at autopsy. Neurologic signs in decreasing frequency were neuropathy (sensory > mixed somatic > autonomic > cranial [especially cranial nerve VIII] > motor), cerebellar ataxia, limbic encephalitis, polyradiculopathy, associated Lambert-Eaton myasthenic syndrome, myopathy, myelopathy, opsoclonus/myoclonus, motor neuronopathy, brachial plexopathy, and aphasia. Nineteen patients had a solely gastrointestinal initial presentation, including gastroparesis, pseudo-obstruction, esophageal achalasia, or other dysmotility. We conclude that seropositivity for ANNA-1 can expedite the diagnosis and treatment of otherwise occult cancer in patients, especially tobacco abusers, with varied neurologic and gastroenterologic presentations. The search for SCLC should not end on discovering a different neoplasm.
 ...
PMID:Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies. 952 Dec 51

Progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1) is a rare, autosomal recessive disorder characterized by onset at age 6-16 years, generalized seizures, incapacitating myoclonus, and variable progression to cerebellar ataxia. The gene that causes EPM1, cystatin B, encodes a cysteine proteinase inhibitor. Only a minority of EPM1 patients carry a point mutation within the transcription unit. The majority of EPM1 alleles contain large expansions of a dodecamer repeat, CCC CGC CCC GCG, located upstream of the 5' transcription start site of the cystatin B gene; normal alleles contain two or three copies of this repeat. All EPM1 alleles with an expansion were resistant to standard PCR amplification. To precisely determine the size of the repeat in affected individuals, we developed a detection protocol involving PCR amplification and subsequent hybridization with an oligonucleotide containing the repeat. The largest detected expansion was approximately 75 copies; the smallest was approximately 30 copies. We identified affected siblings with repeat expansions, of different sizes, on the same haplotype, which confirms the repeat's instability during transmissions. Expansions were observed directly; contractions were deduced by comparison of allele sizes within a family. In a sample of 28 patients, we found no correlation between age at onset of EPM1 and the size of the expanded dodecamer. This suggests that once the dodecamer repeat expands beyond a critical threshold, cystatin B expression is reduced in certain cells, with pathological consequences.
 ...
PMID:A PCR amplification method reveals instability of the dodecamer repeat in progressive myoclonus epilepsy (EPM1) and no correlation between the size of the repeat and age at onset. 952 56

Using a molecular diagnostic approach, we investigated 101 kindreds with autosomal dominant cerebellar ataxias (ADCAs) from the central Honshu island of Japan, including spinocerebellar ataxia type 1 (SCA1), spinocerebellar ataxia type 2 (SCA2), Machado-Joseph disease (MJD), dentatorubral and pallidoluysian atrophy (DRPLA) and spinocerebellar ataxia type 6 (SCA6). In our unselected series, MJD was the most common type of ADCA, accounting for 33.7% followed by DRPLA (19.8%), SCA2 (5.9%) and SCA6 (5.9%). No SCA1 mutations were identified. We analysed the clinical features of six molecular confirmed SCA6 kindreds: in each family, there was an expanded allele in the alpha1A-voltage dependent calcium channel comprising between 23 and 25 CAG repeats. The mean age at onset of symptoms was 43+/-13 years. The clinical features consisted predominantly of cerebellar ataxia, dysarthria and horizontal nystagmus, which was generally consistent with ADCA type 3. However several new clinical features were found in some patients: dramatic anticipation, rapid disease progression, severe ataxia associated with action tremor or action myoclonus, and very early onset, which are not described as the classical features of ADCA type 3.
 ...
PMID:Frequency analysis of autosomal dominant cerebellar ataxias in Japanese patients and clinical characterization of spinocerebellar ataxia type 6. 955 Mar 56

Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant cerebellar ataxia characterized clinically by myoclonus, epilepsy, cerebellar ataxia, choreoathetosis, and dementia with personality change. Histopathologically, DRPLA is characterized by a unique combination of degenerative changes in both the dentatofugal and the pallidofugal systems. Credit for the establishment of DRPLA as an entity is given to Naito and Oyagagi, who first noticed a strong heritability and an age of onset-dependent variability of the clinical features. Most papers on DRPLA research are written in Japanese, and are extensively reviewed here. After the gene was identified in 1994, DRPLA became known as one of the CAG repeat expansion diseases, in which the responsible gene is located on chromosome 12p and its product is called atrophin-1. Classical genetics revealed that DRPLA shows prominent "anticipation" and modern molecular genetics provided a clear explanation for this phenomenon, by demonstrating a strong instability of the expanded CAG repeat length through generations. The impact of gene analysis of DRPLA on the clinical genetics and neurology are discussed. Moreover, possible mechanism(s) underlying the neuronal cell death in DRPLA are discussed in terms of the molecular pathology.
 ...
PMID:Dentatorubral-pallidoluysian atrophy or Naito-Oyanagi disease. 993 95

We report autopsy cases of two brothers with the late infantile form of neuronal ceroid lipofuscinosis (LINCL) and examine apoptotic cell death in autopsied brains. Both patients showed psychomotor developmental delay, cerebellar ataxia, convulsions, visual disturbance and myoclonus, and they became bedridden around the age of 6-7 years. Macular changes, mimicking cherry-red spots, were observed on funduscopy, but conjunctival biopsy failed to disclose storage materials. In these cases, the autopsies demonstrated severe atrophy with neuronal loss and gliosis throughout the brain and spinal cord, except the hypothalamic neurons and motor neurons in the brain-stem and spinal cord, and autofluorescent lipofuscin-like materials of two types, fine granular deposits and coarse round bodies, were stored in the remaining neurons and glial cells, and in the epithelial cells of various visceral organs. Immunostaining for mitochondrial subunit C visualized the fine granular deposits but not the coarse round bodies. The nuclei of neurons and glia cells were stained by in situ nick end labeling, which was more pronounced in the younger case, although the expression of both bcl-2 and bcl-x was not significantly altered in these cases. It is suggested that immunohistochemistry for subunit C may be useful for diagnosis of NCL, and further investigations are necessary to clarify the relationship between LINCL and apoptosis, especially in severely affected cases.
 ...
PMID:Pathological study on sibling autopsy cases of the late infantile form of neuronal ceroid lipofuscinosis. 1008 55

An adult male presenting with acute onset opsoclonus, myoclonus and cerebellar ataxia is being reported. Patient had myoclonus involving limbs and palate. There are only a few reported cases associated with palatal myoclonus. Patient showed gradual spontaneous recovery. Possibility of underlying malignancy was excluded by detailed investigations.
 ...
PMID:Palatal myoclonus in postinfectious opsoclonus myoclonus syndrome : a case report. 1040 40

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant disorder characterized clinically by myoclonus, epilepsy, cerebellar ataxia, choreoathetosis and dementia. Cardinal pathological features of DRPLA are a combined degeneration of both the dentatorubral and the pallidoluysian systems. Although the early sporadic cases were reported by Western neuropathologists, a strong heritability and an age of onset-dependent variability of the clinical features were carefully deduced by Japanese clinicians. The disease is fairly common in Japan, but extremely rare in Caucasians. Since the gene was identified in 1994, DRPLA is known as one of the CAG repeat expansion diseases, in which the responsible gene is located on chromosome 12p and its product is called atrophin 1. DRPLA shows prominent 'anticipation', which is genetically clearly explained by a marked instability of the expanded CAG repeat length during spermatogenesis. Moreover, the instability of the CAG repeat length also seems to occur in the somatic cells, resulting in 'somatic mosaicism'. Possible mechanism(s) underlying the neuronal cell death in DRPLA are discussed in terms of molecular pathological points of view.
 ...
PMID:Molecular pathology of dentatorubral-pallidoluysian atrophy. 1043 7

Progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1; MIM 254800) is an autosomal recessive disorder characterized by seizures, myoclonus and progression to cerebellar ataxia. EPM1 arises due to mutations in the cystatin B (CSTB) gene which encodes a cysteine proteinase inhibitor. Only a minority of EPM1 alleles carry point mutations, while the majority contain large expansions of the dodecamer CCCCGCCCCGCG repeat which is present at two to three copies in normal individuals. The dodecamer repeat is located in the 5' flanking region of the CSTB gene, presumably in its promoter. The pathological repeat expansion results in a reduction in CSTB mRNA, which may be cell specific. To elucidate the mechanism of this reduction of gene expression, we have studied the putative CSTB promoter in vitro. A 3.8 kb fragment, containing the putative promoter with a 600 bp repeat expansion, showed a 2- to 4-fold reduction in luciferase activity compared with an identical fragment with a normal repeat; this reduction was observed only in certain cell types. Introduction of heterologous DNA fragments of 730 and 1000 bp into the normal promoter, instead of the repeat expansion, showed similarly reduced activity. Terminal deletions of the promoter implicate a putative AP-1 binding site, upstream of the repeat, in CSTB transcription activation. We propose that a novel mechanism of pathogenesis, the altering of the spacing of transcription factor binding sites from each other and/or the transcription initiation site due to repeat expansion, is among the causes of reduction in CSTB expression and thus EPM1.
 ...
PMID:Altered spacing of promoter elements due to the dodecamer repeat expansion contributes to reduced expression of the cystatin B gene in EPM1. 1044 45

Ramsay Hunt syndrome (RHS) is a rare condition within the progressive myoclonic epilepsies syndrome (PME), with a triad of action myoclonus, grand mal seizure and severe cerebellar ataxia. There are few reports about the psychiatric disturbances associated with PME or RHS. The present study examines the evidence that RHS may accompany an organic mental syndrome, ethanol's effective suppression of myoclonus, and the possible resultant problem of alcohol dependence in RHS patients. Two brothers with the previous long-standing diagnosis of RHS and their mental symptoms of persecutory delusion and depression are reported, as well as the additional problem of alcohol dependence in one of them. The cerebellar dysfunction found in RHS may be associated with an underlying organic condition. Determination of the relationship between cerebellar dysfunction and psychosis in RHS will require further study. Although the mechanism of the suppression of myoclonus by alcohol remains unclear, patients should be allowed to drink socially, and alcohol consumption should not be totally prohibited. However, effective treatment of the problems of alcohol tolerance, abuse, or dependence requires the cooperation of both neurologists and psychiatrists.
 ...
PMID:Progressive myoclonic epilepsies syndrome (Ramsay Hunt syndrome) with mental disorder: report of two cases. 1059 82

A 36-year-old Japanese woman was admitted to our hospital, because of facial palsy, ophthalmoplegia, cerebellar ataxia, and rhythmic myoclonus of the neck. About a few weeks before admission, she developed symptoms of common cold and general fatigue. Her laboratory data were unremarkable, and her CSF was normal. Serum levels of antibodies to gangliosides were within normal limits. Her MRIs of the brain and neck were normal. Both somatosensory evoked cortical potential study and auditory evoked brainstem response study were normal. She was diagnosed as postinfectious brainstem encephalitis, and the administration of corticosteroid was started. After the treatment, her symptoms improved. To our knowledge, it is rare to see myoclonus to the neck without palatal tremor in patients with brainstem encephalitis.
 ...
PMID:[Rhythmic involuntary movement of the neck in a patient with brainstem encephalitis]. 1065


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>